A number of academic groups and companies have focused on the production of cell-based tumor vaccines by cytokine gene transfer. This approach allows sustained local production of the cytokine and maintains a high concentration of cytokine in the vicinity of the cells. However, gene transfer presents numerous problems. As a practical, product-oriented alternative to genetic modification, we are producing cytokines that are engineered to automatically attach to tumor cells when added exogenously, ex vivo. The immunomodulatory portion of the molecule is thus positioned on the outer cell surface and concentrated in the vicinity of the surface, increasing its potency. These molecules, which we have dubbed "opsonokines", attach to cells through interactions with ubiquitous plasma membrane features. In our Phase 1 SBIR study, a prototype opsonokine-based vaccine has demonstrated excellent antitumor activity in mice. We now continue our in vitro and in vivo studies of the prototype molecule. Over 1,000,000 cases of cancer are diagnosed in the U.S. each year. Current treatment approaches are inadequate. This project seeks to deveop a powerful, practical method for stimulating the immune system to fight this prevalent disease.